Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: Findings from the Nun Study

The development of interventions designed to delay the onset of dementia highlights the need to determine the neuropathologic characteristics of individuals whose cognitive function ranges from intact to demented, including those with mild cognitive impairments. We used the Braak method of staging Alzheimer's disease pathology in 130 women ages 76-102 years who were participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. All participants had complete autopsy data and were free from neuropathologic conditions other than Alzheimer's disease lesions that could affect cognitive function. Findings showed a strong relationship between Braak stage and cognitive state. The presence of memory impairment was associated with more severe Alzheimer's disease pathology and higher incidence of conversion to dementia in the groups classified as having mild or global cognitive impairments. In addition to Braak stage, atrophy of the neocortex was significantly related to the presence of dementia. Our data indicate that Alzheimer's neurofibrillary pathology is one of the neuropathologic substrates of mild cognitive impairments. Additional studies are needed to help explain the variability in neuropathologic findings seen in individuals whose cognitive performance falls between intact function and dementia.